The overall objective of this proposal is to bring together a group of investigators with complementary expertise, whose research will address defined and related areas in the multi-disciplinary field of Transfusion Medicine. The general theme of this SCORE Program Project is t he study of cellular and humoral aspects on immunonomodulation in Transfusion medicine. Immunomodulation may occur as a result of allogeneic blood transfusion. The characterization of such altered and "unwanted", immunity is essential to developing approaches of specific therapeutic intervention. Alternatively, immunomodulation may e intentional as in the treatment of center. The later pertains to the transfusion therapy of allogeneic, immunocompetent cells to induce graft versus leukemia. Collectively, the proposed studies involve unique approaches to characterize allo-and auto-immune responses and further define cell biological features of blood group antigenic targets. In addition, athe SCOR Program will develop novel cellular therapies and examine the mechanisms of their induced immunomodulatory effects. The Program comprises 5 major research projects. Project 1 will access the molecular basis of naturally occurring and pathogenic RBC autoantibodies with respect to their B-cell origin, the role of selection by antigen as opposed to polyclonal activation, and the characterization the odontogenic structures, which remain ill-defined; Project 2 will investigate the anti- Rb alloimmune response at the genetic and serologic level and design inhibitors of anti-Rb antibody - Rh antigen binding; Project 3 pertains to the biology of blood group antigen glycophorus utilizing Chinese hamster ovary cells transfected with glycophorin genes as a model to study both biochemical and immunological aspects of this complex membrane antigen; Project 4 will develop a human umbilical and blood collection, banking and expansion program, which is tailored to the correction of homozygous Sickle Cell Anemia by human umbilical cord cell transplantation; Project 5 will develop in vitro and in vivo animal models relevant to the transfusion of allogeneic human T cells as a novel form of immunomodulatory intervention in cancer therapy. These 5 projects will use complementary approaches and different methodologies to address pathologically related questions, which will accelerate progress through interactions and communication. Together they will bridge disciplines of genetics and biochemistry with a basis in pathophysiology. The information and reagents derived from these studies should be useful in devising immunomodulators in transfusion therapy.